EP2072499B1 - Method for manufacturing thiodiglycolic dialkyl esters - Google Patents

Abstract

Production of thiodiglycolic acid alkyl ester (I), comprises reacting a halogen acetic acid alkyl ester (II) with an aqueous solution of alkali sulfide or alkali hydrogen sulfide in the presence of an aqueous pH-buffer solution in the pH range of 5-8, optionally in the presence of a phase transfer catalyst. Production of thiodiglycolic acid alkyl ester of formula (R-OOC-CH 2-S-CH 2-COO-R) (I), comprises reacting a halogen acetic acid alkyl ester of formula (X-CH 2-COO-R) (II) with an aqueous solution of alkali sulfide or alkali hydrogen sulfide in the presence of an aqueous pH-buffer solution in the pH range of 5-8, optionally in the presence of a phase transfer catalyst. R : 1-10C alkyl; and X : Cl or Br.

Description

The invention relates to a novel process for the preparation of dialkyl C ₁ -C ₁₀ thiodiglycolates.

Thiodiglycolic acid dialkyl esters are important precursors for the production of specialty chemicals, for example for use in electronically conductive polymers.

The synthesis of thiodiglycolic diester has been known in principle for a long time.

1. a) Veresterung von Thiodiglycolsäure mit Alkoholen unter saurer Katalyse.
2. b) Umsetzung von Chloressigsäureester mit Natriumsulfid.

There are essentially two ways to synthesize thiodiglycolic acid dialkyl ester:

1. a) Esterification of thiodiglycolic acid with alcohols under acidic catalysis.
2. b) Reaction of chloroacetic acid ester with sodium sulfide.

A major disadvantage of variant a) is that for the esterification of thiodiglycolic acid with alcohols with the aid of hydrochloric acid ( Schulze, Zeitschrift fur Chemie 1865, p. 78 ) or with the aid of sulfuric acid ( Seka, Reports 58, 1925, p. 1786 ) crystalline thiodiglycolic acid is needed. This means that the highly water-soluble thiodiglycolic acid must be separated from the water phase. This always leaves a portion of thiodiglycolic acid in the mother liquor and also falls in the isolation as a solid, the thiodiglycolic acid together with inorganic salts, so that it must be recrystallized again. Esterification from the aqueous solution therefore gives unsatisfactory results ( US 2,425,225 ).

To avoid the elaborate isolation of thiodiglycolic acid as a solid, is in the US 2,425,225 describes a method in which the thiodiglycolic acid is extracted directly from the aqueous phase with the alcohol to be esterified. However, this process only works with alcohols having more than three carbon atoms and is therefore unsuitable for the synthesis of thiodiglycolic acid methyl ester, ethyl ester and propyl ester, since the corresponding alcohols having less than four carbon atoms are completely soluble in water and therefore do not function as extractants can.

A particular difficulty in the reaction of chloroacetic acid ester with sodium sulfide is that sodium sulfide is a very strong base, while chloroacetic acid esters are very pH sensitive and readily saponify.

If an aqueous sodium sulfide solution is introduced into methyl chloroacetate, only moderate yields of methyl thiodiglycolate are obtained on account of the saponification of the educt and / or the product. In the WO 00/45451 is given in the implementation of bromoacetic acid ethyl ester with sodium sulfide, a yield of 39%.

One way to avoid the saponification of the chloroacetic acid ester, as in the US 2,262,686 described to carry out the reaction in an inert solvent such as acetone. In this anhydrous variant for the synthesis of Thiodiglycolsäureester anhydrous sodium sulfide is required, which is significantly more expensive than hydrous, and the reaction time is disproportionately long with 15 to 20 hours boiling at reflux.

The object of the present invention was to provide a process for preparing a thiodiglycolic acid dialkyl ester which gives the desired product in a simplified manner and with a better yield than in the prior art.

Surprisingly, it has been found that by adjusting suitable reaction conditions, the reaction of methyl chloroacetate with alkali metal sulfide or alkali metal hydrogen sulfide to dimethyl thiodiglycolate in aqueous solution yields very high yields. It is crucial that the sulfide compound reacts quickly and thus the pH in the solution in the range 5 <pH <8 is maintained.

The invention therefore provides a process for preparing alkyl thiodiglycolates of the general formula (I)

R-OOC-CH2-S-CH2-COO-R (I),

where R is a radical of branched or unbranched C ₁ to C ₁₀ -alkyl,
characterized in that a haloacetic acid alkyl ester of the general formula (II)

X-CH 2 -COO-R (II),

where X is a chlorine or bromine atom and R has the meaning given for compounds of the formula (I),
is reacted with an aqueous solution of alkali metal sulfide or alkali metal hydrogen sulfide in the presence of an aqueous pH buffer solution in the pH range between 5 and 8.

Preferably, the aqueous buffer solution is a dialkalihydrogenphosphate or alkali metal dihydrogenphosphate or ammonium acetate or ammonium chloride buffer solution. Examples of dialkalihydrogenphosphate are K ₂ HPO ₄ or Na ₂ HPO ₄ , examples of alkali metal hydrogenphosphate are KH ₂ PO ₄ and NaH ₂ PO ₄ .

As the sulfide source, aqueous solutions of both alkali sulfide (sodium or potassium sulfide) and alkali hydrogen sulfide (sodium or potassium hydrogen sulfide) can be used. The concentration of the aqueous alkali sulfide solution is between 5 and 20% by weight and that of the alkali metal hydrogen sulphide solution is between 5 and 50% by weight.

The metered addition of the reagents to the aqueous buffer solution may be carried out with stirring in a manner known per se, e.g. in a heatable jacketed vessel via pumps, through separate lines or via a static mixer.

The C ₁ -C ₁₀ -haloacetic acid alkyl ester is usually added together with the alkali metal or alkali metal hydrogensulfide in a molar ratio of between 1: 1 and 3: 1. This molar ratio is preferably 2: 1. The metered addition may take place simultaneously or in portions, but preferably simultaneously.

The simultaneous dosage is usually over a period of 0.5 to 24 hours. The temperature at which the dosage takes place should be in the range between 10 and 60 ° C, preferably 20 to 40 ° C.

Preferably, the reaction is carried out in the presence of a phase transfer catalyst. The commercially available catalysts are preferably tetrabutylammonium chloride, tributylmethylammonium chloride, methyltrioctylammonium chloride, methyltridecylammonium chloride, polyethylene glycol 400-40,000, crown ethers, tris [2- (2-methoxyethoxy) ethyl] amines or trialkylphosphonium salts. The phase transfer catalyst used is particularly preferably tetrabutylammonium chloride or polyethylene glycol 400.

Care must be taken that the pH is maintained between 5 and 8 during the reaction.

After the reaction, the crude product is separated from the aqueous buffer solution. This can e.g. done by extraction. For this purpose, the reaction solution is mixed with a water-immiscible solvent and the aqueous phase separated from the organic phase. The organic phase can then be subsequently, e.g. by distillation, the extractant are separated. The residue contains the desired product in yields of 88 to 95% of theory.

As extracting agents for separating the crude product from the aqueous buffer solution, it is possible to use branched or unbranched C ₂ -C ₄ -dialkyl ethers, such as diethyl ether (DEE) and methyl tert-butyl ether (MTBE), or branched or unbranched dialkyl ketones, such as methyl isobutyl ketone (MIBK ), or branched or unbranched C ₄ -C ₁₀ hydrocarbons such as pentane, hexane, heptane or Cyclohexane, or aromatic compounds such as benzene, toluene, xylene or dichlorobenzene can be used. Preferably, toluene is used as the extraction agent.

By the process according to the invention, thiodiglycolic acid dialkyl esters with C ₁ -C ₁₀ -alkyl radicals in the ester parts can be prepared by using the corresponding C ₁ -C ₁₀ -halogacetic acid alkyl ester. The C ₁ -C ₄ -alkyl esters, ie, thiodiglycolic acid dimethyl, thiodiglycolic acid diethyl, thiodiglycolic acid dipropyl or thiodiglycolic acid dibutyl ester, are preferably prepared. Particularly preferred are thiodiglycolic acid and diethyl thioic acid.

The Thiodiglycolsuredialkylester obtained by the described method can be further processed directly without purification by distillation. Due to the almost quantitative and rapid conversion of sodium sulfide, neither the exhaust air nor the wastewater contains appreciable amounts of hydrogen sulfide.

The following examples are intended to further illustrate the invention.

example 1

17.9 g of sodium dihydrogen phosphate dihydrate were dissolved in 84.2 g of water in a 1 ltr. Jacketed glass reactor (pH = 3.9) and adjusted to pH = 6.0 with 6.7 g of sodium hydroxide solution (32% strength). The buffer solution was heated to 33 ° C and treated with 13.0 g of tributylmethylammonium chloride solution (75% in water) and 40.0 g of methyl chloroacetate. Simultaneously, 611.2 g of sodium sulfide solution (16% strength in water) and 182.1 g of methyl chloroacetate were added within 2 h at 30-35 ° C. Subsequently, a further 19.3 g of sodium sulfide solution (16% in water) were added and stirred at 33 ° C for 1 h. The reaction solution was added with 130 ml of toluene, stirred vigorously and then the lower phase was separated. After distilling off the toluene in vacuo at about 300 mbar 226.6 g of a clear liquid with 93% dimethyl thiodiglycolate and 6% toluene were obtained. This corresponds to a theoretical yield of 93%.

Example 2

In a 1 liter double-walled glass reactor, 35.8 g of sodium dihydrogen phosphate dihydrate were dissolved in 168.4 g of water (pH = 3.9) and adjusted to pH = 7.0 with 24.4 g of sodium hydroxide solution (32% strength). The buffer solution was heated to 33 ° C and treated with 13.0 g of tributylmethylammonium chloride solution (75% in water) and 40.0 g of methyl chloroacetate. Simultaneously, 269.8 g of sodium bisulfite solution (26% in water) and 182.1 g of methyl chloroacetate were added within 2 h at 30-35 ° C. The pH = 7 was maintained by simultaneous addition of sodium hydroxide solution (32% in water). Subsequently, a further 8.5 g of sodium bisulfite solution (26% in water) were metered in and stirred at 33 ° C. for 1 h. The reaction solution was mixed with 130 ml of toluene and stirred vigorously. Subsequently, the lower phase was separated. After distilling off the toluene in vacuo at about 300 mbar, 236.4 g of a clear liquid with 91% dimethyl thiodiglycolate and 6% toluene were obtained. This corresponds to a theoretical yield of 95%.

Example 3

17.9 g of sodium dihydrogen phosphate dihydrate were dissolved in 84.2 g of water in a 1 liter double-walled glass reactor (pH = 3.9) and adjusted to pH = 6.0 with 6.7 g of sodium hydroxide solution (32% strength). The buffer solution was heated to 33 ° C and treated with 13.0 g of tributylmethylammonium chloride solution (75% in water) and 40.0 g of methyl chloroacetate. Simultaneously, 611.2 g of sodium sulfide solution (16% strength in water) and 182.1 g of methyl chloroacetate were added within 2 h at 30-35 ° C. Subsequently, a further 19.3 g of sodium sulfide solution (16% in Water) and stirred for 1 h at 33 ° C. The reaction solution was mixed with 130 ml of toluene and stirred vigorously. Subsequently, the lower phase was separated. After distilling off the toluene in vacuo at about 300 mbar 226.6 g of a clear liquid with 93% dimethyl thiodiglycolate and 6% toluene were obtained. This corresponds to a theoretical yield of 93%.

Example 4

In a 1 ltr. Jacketed glass reactor, 35.8 g of sodium dihydrogen phosphate dihydrate were dissolved in 168.4 g of water (pH = 3.9) and adjusted to pH = 6.0 with 11.4 g of sodium hydroxide solution (32% strength). The buffer solution was heated to 33 ° C and treated with 13.0 g of polyethylene glycol 400 and 40.0 g of methyl chloroacetate. Simultaneously, 611.2 g of sodium sulfide solution (16% strength in water) and 182.1 g of methyl chloroacetate were added within 2 h at 30-35 ° C. Subsequently, a further 19.3 g of sodium sulfide solution (16% in water) were metered in and stirred at 33 ° C. for 2 h. The reaction solution was mixed with 130 ml of toluene and stirred vigorously. Subsequently, the lower phase was separated. After distilling off the toluene in vacuo at about 300 mbar, 227.2 g of a clear liquid containing 88% dimethyl thiodiglycolate, 1% methyl thioglycolate, 1% ethyl chloroacetate and 6% toluene were obtained. This corresponds to a theoretical yield of 90%.

Example 5

In a 1 ltr. Jacketed glass reactor, 15.8 g of glacial acetic acid were dissolved in 168.4 g of water (pH = 2.3) and adjusted to pH = 6.0 with 19.0 g of aqueous ammonia solution (26% strength). The buffer solution was warmed to 33 ° C and treated with 16.0 g of tributylmethylammonium chloride solution (75% in water) and 40.0 g of methyl chloroacetate. Simultaneously, 611.2 g of sodium sulfide solution (16% strength in water) and 182.1 g of methyl chloroacetate were added within 2 h at 30-35 ° C. Subsequently, a further 19.3 g of sodium sulfide solution (16% in water) were added and stirred at 33 ° C for 1 h. The reaction solution was mixed with 130 ml of toluene and stirred vigorously. Subsequently, the lower phase was separated. After distilling off the toluene in vacuo at about 300 mbar 223.8 g of a clear liquid with 92% dimethyl thiodiglycolate and 6% toluene were obtained. This corresponds to a theoretical yield of 90%.

Example 6

In a 1 liter double-walled glass reactor, 35.8 g of sodium dihydrogen phosphate dihydrate were dissolved in 168.4 g of water (pH = 3.9) and adjusted to pH = 6.0 with 12.2 g of sodium hydroxide solution (32%). The buffer solution was heated to 33 ° C and treated with 13.0 g of tributylmethylammonium chloride solution (75% in water) and 40.0 g of ethyl chloroacetate. Simultaneously, 611.2 g of sodium sulfide solution (16% in water) and 275.3 g of ethyl chloroacetate were added within 2 h at 30-35 ° C. Subsequently, a further 19.3 g of sodium sulfide solution (16% in water) were added and stirred at 33 ° C for 1 h. Subsequently, a further 19.3 g of sodium sulfide solution (16% in water) were metered in and stirred at 33 ° C. for 2 h. The reaction solution was mixed with 130 ml of toluene and stirred vigorously. Subsequently, the lower phase was separated. After distilling off the toluene in vacuo at about 300 mbar, 277.2 g of a clear liquid with 90% diethyl thiodiglycolate and 9% toluene were obtained. This corresponds to a theoretical yield of 95%.

Claims (10)

1. Process for preparing alkyl thiodiglycolates of the general formula (I)
   
           R-OOC-CH2-S-CH2-COO-R     (I)
   
   where R is a of branched or unbranched C₁ to C₁₀-alkyl radical,
   characterized in that an alkyl haloacetate of the general formula (II)
   
           X-CH2-COO-R     (II)
   
   where X is a chlorine or bromine atom and R is as defined for compounds of the formula (I)
   is reacted with an aqueous solution of alkali metal sulphide or alkali metal hydrogensulphide in the presence of an aqueous pH buffer solution in the pH range between 5 and 8.
2. Process according to Claim 1, characterized in that the process is performed in the presence of a phase transfer catalyst.
3. Process according to either of Claims 1 and 2, characterized in that the aqueous buffer solution comprises a dialkali metal hydrogenphosphate buffer, an alkali metal dihydrogenphosphate buffer, a sodium hydrogencarbonate buffer, an ammonium acetate buffer or an ammonium chloride buffer.
4. Process according to any of Claims 1 to 3, characterized in that the pH range is between 6 and 8.
5. Process according to any of Claims 1 to 4, characterized in that the aqueous alkali metal sulphide solution used is an aqueous sodium sulphide solution having a content between 5 and 30% by weight or an aqueous sodium hydrogensulphide solution having a content between 5 and 50% by weight.
6. Process according to any of Claims 1 to 5, characterized in that the alkyl haloacetate of the formula (II) is a methyl, ethyl, propyl, butyl, pentyl, hexyl or cyclohexyl chloroacetate or a methyl, ethyl, propyl, butyl, pentyl, hexyl or cyclohexyl bromoacetate.
7. Process according to any of Claims 1 to 6, characterized in that the alkyl haloacetate of the formula (II) and the alkali metal sulphide or alkali metal hydrogensulphide solution are metered in simultaneously in a molar ratio of 1:1 to 3:1 relative to one another.
8. Process according to any of Claims 1 to 7, characterized in that the temperature of the reaction solution is in the range of 0 to 60°C.
9. Process according to any of Claims 2 to 8, characterized in that the phase transfer catalyst used is tetrabutylammonium chloride, tributyl-methylammonium chloride, methyltrioctylammonium chloride, methyltridecylammonium chloride, polyethylene glycol 400 - 40 000, crown ethers, tris[2-(2-methoxyethoxy)ethyl]amine or a trialkyl-phosphonium salt.
10. Process according to any of Claims 1 to 9, characterized in that the dialkyl C₁-C₁₀-thiodiglycolate is removed from the aqueous reaction solution with a water-immiscible organic solvent.